TABLE OF CONTENT

TOPIC PAGE

1. GLOMERULAR DISEASES 2
1a. NEPHROTIC VS NEPHRITIC SYNDROME 2

2. IgA NEPHROPATHY VS POST-INFECTIOUS 3

GLOMERULONEPHRITIS

3. Post-streptococcal glomerulonephritis 3

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DIFFERENTIAL DIAGNOSIS OF GLOMERULAR DISEASES - urine ACR: used to screen for diabetic nephropathy
- microalbuminuria: ACR ≥2.0mg/mmol
-Marker of vascular endothelial function
- An important prognostic marker for kidney disease in DM
and HTN
-Microalbuminuria is the earliest sign of diabetic
nephropathy
- Composition of normal total urine protein
- Upper limit of normal daily excretion of total protein is
150 mg/d
- Upper limit of normal daily excretion of albumin is 30
mg/d
- The other normally excreted proteins are either filtered
low molecular weight proteins (such as
immunoglobulin light chains or β-2 microglobulin) or
NEPHROTIC VS NEPHRITIC SYNDROME proteins secreted by the tubular epithelial cells
(e.g. Tamm-Horsfall mucoprotein)

Investigations
- urine R&M, C&S, urea, Cr
- further workup (if degree of proteinuria >0.5 g/d, casts,
and/or hematuria)
- CBC, glucose, electrolytes, 24 h urine protein, and Cr
- Urine and serum immunoelectrophoresis,
abdominal/pelvic U/S
- Serology: ANA, RF, p-ANCA (MPO), c-ANCA (PR3), Hep B,
Hep C, HIV, ASOT
• indications for nephrology referral
- Generally, if there is “heavy” proteinuria (ACR >30
mg/mmol), should refer to nephrologist
- Definitely if there is nephrotic syndrome
GLOMERULAR VS NON-GLOMERULAR HEMATURIA

1. NEPHROTIC SYNDROME (TN 2018)

- PROTEINURIA
Hallmark of nephrotic syndromes
- Composition of normal urine protein: albumin, lower
molecular proteins (such as immunoglobulin
light chain) or proteins secreted by the tubular epithelial
cells (e.g. Tamm-Horsfall mucoprotein)

- 24 h urine protein: gold standard to assess degree of

proteinuria

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NEPHROTIC $YNDROMES & THEIR ASSOCIATIONS:
(Tiki-Taka)
 CHILDREN  Minimal change disease
 ADULTS & CANCERS "LYMPHOMA" MEMBRANOUS
 HEPATITIS C  MEMBRANOPROLIFERATIVE
 HIV, HEROIN USE  FOCAL SEGMENTAL
 UN-CLEAR  MESANGIAL

2.
ACUTE NEPHRITIC SYNDROME (TN 2018)
IgA NEPHROPATHY VS POST-INFECTIOUS
- Etiology can be divided into low and normal complement GLOMERULONEPHRITIS ( UWORLD)
levels
• frequently immune-mediated, with Ig and C3 deposits - Is hematuria with concomitant URTI (Synpahryngitic).
found in GBM - Treat with ACEI or ARBS.
- Biopsy is gold standard and shows diffuse mesangial
proliferation on light microscope and granular deposits in
Clinical/Lab Features the messangium and glomerular capillary wall on electron
- proteinuria (but <3.5 g/1.73 m2/d) microscope.
- abrupt onset hematuria (microscopic or macroscopic) -MCC of GN in adults
- azotemia (increased Cr and urea) - 1-3days after an URTI
- RBC casts and/or dysmorphic RBCs in urine - Recurrent episodes of gross hematuria
- oliguria, HTN (due to salt and water retention) - Serum compliment: NORMAL
- peripheral edema/puffy eyes IgA nephropathy may also follow GI infection
- smoky urine
Treatment
• Depends on etiology - Post-streptococcal glomerulonephritis
• Pulse steroid therapy and other immunosuppression, BP can also occur after streptococcal skin infection
control, monitoring for progression to end - 1-3wks after pharyngitis(10days) and Impetigo (21days)
stage renal disease
IgA NEPHROPATHY VS POST-INFECTIOUS GLOMERULONEPHRITIS

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A 22-year-old man comes to the urgent care clinic young adult men. Serum complement levels tend to be
complaining of dark urine he noticed earlier this morning. normal with mesangial lgA deposits seen in kidney biopsy.
He is recovering from an upper respiratory tract infection Patients can have a benign course or develop rapidly
that started 4 days ago. The patient's temperature is 37.1 progressive GN or nephrotic syndrome.
C (98.9 F), blood pressure is 145/92 mm Hg, pulse is
80/min, and respirations are 14/min. Physical examination (Choice A) Acute interstitial nephritis is an acute
shows no skin rash and no joint abnormalities. inflammatory process involving the renal tubules and
interstitium following exposure to a drug (eg, antibiotics,
Laboratory results are as follows: nonsteroidal anti-inflammatory drugs, proton-pump
Urinalysis inhibitors). Other findings can include fever, skin rash,
Glucose: Negative eosinophilia, eosinophiluria, or white blood cell casts.
Protein: 1+ However, this patient lacks other findings (eg, fever, skin
Ketones: Negative rash) and has no history of drug exposure; this makes
Leukocyte esterase: Negative acute interstitial nephritis less likely.
Nitrites: Negative
White blood cells: 3-6/hpf (Choice C) Alport syndrome is an X-linked defect in
Red blood cells: 30-50/hpf collagen-IV formation and presents with hearing loss,
Casts: Red blood cells ocular abnormalities, hematuria, and progressive renal
Serum chemistry insufficiency. Kidney biopsy usually shows thinning of the
Serum sodium: 138 mEq/L glomerular basement membrane. However, post-URI gross
Serum potassium: 4.5 mEq/L hematuria is not typically seen in Alport syndrome.
Bicarbonate: 22 mEq/L
Blood urea nitrogen: 18 mg/dL (Choices D and F) Anti-glomerular basement membrane
Serum creatinine: 1.4 mg/dL (anti-GBM) disease is due to anti-GBM antibodies against
Serum complement levels: (C3 and C4) are within normal collagen IV (alpha-5 chain) damaging the glomeruli and
limits, and other serological alveolar lining. Anti-GBM disease manifests as either a
workup is pending. renal limited process (rapidly progressive GN) or alveolar
hemorrhage (pulmonary renal syndrome). Goodpasture's
Which of the following is the most likely diagnosis? syndrome refers to a pulmonary-renal syndrome that is a
A. Acute interstitial nephritis manifestation of anti-GBM disease. This patient's absence
B. Acute postinfectious glomerulonephritis of significantly elevated creatinine makes this less likely.
C. Alport syndrome
D. Anti-glomerular basement membrane disease (Choice E) Benign recurrent hematuria, also known as thin
E. Benign recurrent hematuria basement membrane nephropathy, is a benign familial
F. Goodpasture's syndrome condition that presents as isolated microscopic hematuria.
G. Henoch-Schonlein purpura However, it does not worsen kidney function or present as
H. IgA nephropathy gross hematuria after a URI.
I. Lupus nephritis
(Choice I) Lupus nephritis can present as nephritic
syndrome, nephrotic syndrome, rapidly progressive GN, or
pulmonary-renal syndrome. Patients usually have low
This patient's gross hematuria is associated with an upper complement levels (C3 and C4) and positive lupus
respiratory tract infection (URI), hypertension, proteinuria, antibodies (anti-nuclear antibodies, anti-dsDNA. anti-Smith
red blood cell casts, and acute kidney injury. This suggests antibodies). This patient's normal serum complement
glomerulonephritis (GN). After a URI, GN can occur due to levels make this unlikely.
lgA nephropathy and postinfectious GN. Postinfectious GN
typically occurs 10-21 days after a URI (post-pharyngitic) Educational objective:
and is more common in children. Adults can be lgA nephropathy is the most common cause of
asymptomatic or develop acute nephritic syndrome. glomerulonephritis in adults. Patients have recurrent
Laboratory studies usually show low C3 complement and episodes of gross hematuria, usually within 5 days after an
elevated anti-streptolysin 0 and/or anti-DNAse B. This upper respiratory tract infection (synpharyngitic
patient's normal serum complements and hematuria time presentation). lgA nephropathy is differentiated from post-
course (4 days after URI) are not consistent with infectious glomerulonephritis based on earlier onset of
postinfectious GN (Choice B). lgA nephropathy is the most upper respiratory tract infection-related
common cause of GN in adults. Patients can have glomerulonephritis and normal serum complement levels.
recurrent Kidney biopsy can also help differentiate these 2
episodes of hematuria usually within 5 days of a URI processes.
(synpharyngitic ). lgA nephropathy is more common in

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 • prognosis: 50% recovery with early treatment, depends
on underlying cause
QUICK NOTES

* IgA NEPHROPATHY = BERGER's DISEASE:

______________________________________
. Painless recurrent hematuria.
. ASIAN pt.
. H/O of very recent viral upper RTI.
. Dx: Best initial test: ++ IgA
. Dx: Most accurate test: RENAL BIOPSY IS ESSENTIAL
. Normal complement levels.
. Tx: Steroids.

* POST-STREPTOCOCCAL GLOMERULONEPHRITIS = PSGN:

________________________________________________
. Dark urine "Tea-colored or cola-colored".
. Periorbital edema & hypertension.
. H/O of Throat or skin infections 10 - 20 days ago.
. Dx: Best initial test: Anti-streptolysin O test "ASLO",
. Anti-DNase & Antihyaluronidase.
. Low complement levels.
. Dx: Most accurate test: R. biopsy sh'd n't be done bec.
blood tests r suffecient.
. Tx: Antibiotics e.g. PENICILLIN.
. CONTROL HYPERTENSION & FLUID OVERLOAD with
diuretics.

RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

(TN 2018)
subset of nephritic syndrome in which the clinical course
proceeds over weeks to months
• clinical diagnosis, not histopathological
• any cause of GN can present as RPGN (except minimal
change disease)
• additional etiologies seen only as RPGN: anti-GBM
Disease and granulomatosis with polyangiitis
(previously called Wegener’s granulomatosis)
• crescentic GN (identified by pathology) results from
proliferation of parietal epithelial cells and is the
most aggressive form of glomerular disease

Clinical/Lab Features
• fibrous crescents typically present on renal
histopathology
• RBC casts and/or dysmorphic RBCs in urine
• classified by immunofluorescence staining
• Type I: Anti-GBM mediated (15% of cases)
• Type II: Immune Complex Mediated (24% of cases)
• Type III: Non-Immune Mediated (60% of cases)
• Type IV: Double Antibody Positive

Treatment and Prognosis

• treatment: underlying cause for postinfectious;
corticosteroids + cyclophosphamide or other cytotoxic
agent + plasmaphoresis in management of cases such as
Anti-GBM Ab